NAM is the official provider of online scientific reporting for the
8th International AIDS Society Conference on HIV Pathogenesis, Treatment
and Prevention (IAS 2015), which will take place in Vancouver, Canada,
19th-22nd July 2015.

The VOICE trial randomised 5029 women from three sites in
South Africa, two in Zimbabwe and one in Uganda, although Durban in South Africa,
with 3110 enrolled, provided more than half the participants. The women were
randomised to use one of three prevention methods or two placebos (dummy
methods):

daily Truvada
(tenofovir plus emtricitabine) as PrEP;

daily tenofovir as PrEP;

a daily placebo pill looking like Truvada;

a tenofovir-containing gel, similar to that used
in the CAPRISA 004 study, to be used as a vaginal microbicide;

an inert gel as a placebo microbicide.

The tenofovir
oral PrEP arm, and the tenofovir
vaginal gel and placebo arms of the trial were stopped due to futility in September
and November 2011 respectively. ('Futility' means that the trial's data and
safety monitoring board, which sees who is receiving treatment and who is
receiving placebo, realised that there was no possibility that continuing the
trial would produce a positive result.) The Truvada
PrEP and placebo-pill arms, however, were continued.

But the conference heard today that Truvada had also not proven effective in
preventing HIV and that therefore all three methods had proved no better than
placebo.

Results: infections

This was a group of relatively young (average age 25) and
largely unmarried (79% single) women. Retention – keeping trial subjects
attending appointments – was good, with only 9% dropping out of the study.

Self-reported condom use at last vaginal sex was very high,
at 85%, but needs to be regarded with a degree of scepticism given the extreme disconnect
(see below) between self-reported and actual adherence. Quite a high proportion
of women (17%) reported anal sex in the last three months.

During the trial 334 of the women tested HIV positive, but
22 of them turned out to have entered the trial while actually having been
infected with HIV very shortly beforehand and so not testing HIV antibody
positive. This means 312, or 6.2% of participants became infected during the trial,
which translates into an annual incidence rate (infection rate per year) of
5.7%, with strong geographical variance by site from 0.8% to 9.9%.

None of the three prevention methods resulted in fewer HIV
infections than placebo. In the women using the tenofovir-gel microbicide there
were 15% fewer infections versus placebo, but this was not statistically
significant. In the oral PrEP arms there were actually more infections in women
taking PrEP compared to placebo. Women taking Truvada were 4% more likely and
women taking tenofovir alone 49% more likely to become HIV positive than women
taking placebo and in the latter case this was almost statistically significant
(95% confidence interval 0.97-2.29, p = 0.07).

Results: adherence

Adherence to the pills or microbicide, according to two
different methods of self-report, was 90%. However analysis of drug levels in
the blood and in the case of the microbicide in vaginal fluids showed a very different
story, and one that is starting to be familiar in PrEP and microbicide studies:
only 28-29% of women taking tenofovir or
Truvada PrEP had measurable drug levels in their blood, and only 22% of women
using tenofovir microbicide.

The assays used could detect whether drug had been taken in
the last two days on oral PrEP, and used in the last three days in the case of
microbicide gel, so some may possibly have used PrEP or microbicide some time
since the previous trial visit, but 50 to 58% of women, depending on which group
they were in, had no detectable drug in their blood at any trial visit.

Women who were married, were aged over 25, or who had a
primary partner aged over 28, were more likely to have detectable drug levels. In
particular, married women were 2.6 times more likely to have detectable drug.

Married women were also very considerably less likely to acquire
HIV than unmarried women: annual incidence in married women in South Africa was
0.9%, compared with 7.5% in unmarried women. Women over 25 were half as likely
to acquire HIV as women under 25 (annual incidence in South African women were
4.7% and 8.7% respectively).

These results seem to back up what was found in the
similarly ineffective FEM-PrEP trial
and in a
recent pilot trial of PrEP in young gay men: being young seems to make it
particularly difficult to adhere to these biomedical prevention methods and, as
the investigators comment, suggests that "products that are long-lasting and
require minimal daily adherence may be more suitable for this population."
They also called for more social
research to determine which populations might benefit.

In addition, as an audience member commented, the benefits
of joining a trial like VOICE in a resource-poor setting – health monitoring,
condoms, the ability to talk about sex with a counsellor, and so on – may be so
large as to make the disclosure of non-adherence, and of other lapses such as
not using condoms, almost impossible in the perception of the participants.

NAM is partnering with gTt (Barcelona), GAT (Lisbon) and LILA (Como) to deliver the CROI 2013 bulletins, which have also been made possible thanks to support from Bristol-Myers Squibb. NAM’s wider conference news reporting services have been supported by Abbott, Boehringer Ingelheim, Janssen, Roche and ViiV Healthcare. The funders have no editorial control over the content of the materials.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.